Cancer and subsequent metastatic disease continue to be a significant source of mortality. Treatment and outcome are largely determined by whether the cancer has disseminated or metastasized, and once the cancer is no longer locally confined, patient prognosis is poor. We have few treatment opportunities for patients once they have metastases, typically resulting in palliative care. This project aims to study the Bone Morphogenetic Protein (BMP) pathway in metastatic prostate cancers, which preliminary data indicates may be a target for therapy and could potentially revolutionize the management of metastatic disease. This proposal focuses on three key areas: 1) Skeletal metastases, which may be dependent upon BMP signaling to persist. 2) Myeloid cell suppression of anti-tumor immune responses, which may be BMP dependent. 3) Restoration of the adaptive immune system to kill tumor cells through targeting in vivo the myeloid immune suppressive cells BMP signaling. Use of small molecule BMP antagonists developed by VA scientists originally for cardiovascular medicine may hold promise as novel treatments in the fight against metastatic cancers.